Evidence map›Paper›PMID 33292650›Full record

ArticleEye and vision (London, England)2020

The anti-scarring effect of corneal stromal stem cell therapy is mediated by transforming growth factor β3.

Lin Weng, James L Funderburgh, Irona Khandaker, Moira L Geary, Tianbing Yang, Rohan Basu, Martha L Funderburgh, Yiqin Du, Gary Hin-Fai Yam

Open access · diamondAbstract read
In one paragraph

Article in Eye and vision (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.2field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 23 citations in OpenAlex.

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  19. Regenerative therapy for the Cornea.Progress in retinal and eye research · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 2 countries.

Lin WengDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
James L FunderburghDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Irona KhandakerDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Moira L GearyDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Tianbing YangDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Rohan BasuDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Martha L FunderburghDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Yiqin DuDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Gary Hin-Fai YamDepartment of Ophthalmology, University of Pittsburgh School of medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA. yamg@pitt.edu.ORCID http://orcid.org/0000-0002-8445-3669
University of Pittsburgh · US

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
Stem Cells for Corneal EngineeringR01EY016415 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DU, YIQIN · 2006 to 2018
$4.5M
Department of Defence, US W81WH-19-1-0778NEI NIH HHS P30 EY008098NEI NIH HHS R01 EY016415Research to Prevent Blindness Stein Innovator Award
6 · The paper itself

Abstract

backgroundCorneal stromal stem cells (CSSC) reduce corneal inflammation, prevent fibrotic scarring, and regenerate transparent stromal tissue in injured corneas. These effects rely on factors produced by CSSC to block the fibrotic gene expression. This study investigated the mechanism of the scar-free regeneration effect.

methodsPrimary human CSSC (hCSSC) from donor corneal rims were cultivated to passage 3 and co-cultured with mouse macrophage RAW264.7 cells induced to M1 pro-inflammatory phenotype by treatment with interferon-γ and lipopolysaccharides, or to M2 anti-inflammatory phenotype by interleukin-4, in a Transwell system. The time-course expression of human transforming growth factor β3 (hTGFβ3) and hTGFβ1 were examined by immunofluorescence and qPCR. TGFβ3 knockdown for > 70% in hCSSC [hCSSC-TGFβ3(si)] was achieved by small interfering RNA transfection. Naïve CSSC and hCSSC-TGFβ3(si) were transplanted in a fibrin gel to mouse corneas, respectively, after wounding by stromal ablation. Corneal clarity and the expression of mouse inflammatory and fibrosis genes were examined.

resultshTGFβ3 was upregulated by hCSSC when co-cultured with RAW cells under M1 condition. Transplantation of hCSSC to wounded mouse corneas showed significant upregulation of hTGFβ3 at days 1 and 3 post-injury, along with the reduced expression of mouse inflammatory genes (CD80, C-X-C motif chemokine ligand 5, lipocalin 2, plasminogen activator urokinase receptor, pro-platelet basic protein, and secreted phosphoprotein 1). By day 14, hCSSC treatment significantly reduced the expression of fibrotic and scar tissue genes (fibronectin, hyaluronan synthase 2, Secreted protein acidic and cysteine rich, tenascin C, collagen 3a1 and α-smooth muscle actin), and the injured corneas remained clear. However, hCSSC-TGFβ3(si) lost these anti-inflammatory and anti-scarring functions, and the wounded corneas showed intense scarring.

conclusionThis study has demonstrated that the corneal regenerative effect of hCSSC is mediated by TGFβ3, inducing a scar-free tissue response.

Indexed as

Corneal stromal stem cellsCornea wound healingFibrosisInflammationTGFβ3

Identifiers

PMID33292650
PMCPMC7607765
OpenAlexW3096875125

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.